The overall objective of this SBIR project is the development of a rapid, high resolution optical method for in vivo imaging with a specific emphasis on identifying vulnerable plaque associated with cardiovascular disease. The approach uses a patent pending harmonic detection method combined with swept source optical coherence tomography for subsurface imaging of the interior walls of arteries. This method will provide important improvements over present optical coherence tomography technologies and can easily be used with fiber optics allowing coupling into endoscopes, catheters and similar devices. Harmonic detection overcomes an important disadvantage of frequency domain optical coherence tomography by achieving noise-limited removal of the complex conjugate ambiguity and other artifacts. Our approach provides better artifact rejection ratios with simpler instrumentation than other methods. With removal of these artifacts, image quality is improved, depth range is increased and the full, complex phase information is obtained. By using this harmonic detection method with swept source optical coherence tomography, the requirements for fast in vivo imaging of arterial and venous structures can be met and provide a useful method for imaging vulnerable plaque. The harmonic detection method and its benefits are applicable to frequency domain optical coherence tomography in general and can be applied to other biomedical research and medical imaging applications where optical coherence tomography has been used or is under development. In Phase II of this project, further improvements to the harmonic detection instrumentation will be made, transitioning from bench-top instrumentation using bulky, non-optimal off-the-shelf components, to a compact, commercial prototype. A currently available commercial swept source optical coherence tomography instrument will be modified to incorporate our harmonic detection technology. The applicability of this approach to biomedical imaging will be demonstrated by imaging diseased arterial segments, ex vivo and showing that our approach is competitive with time domain and other frequency domain optical coherence tomography approaches. PUBLIC HEALTH RELEVANCE: In vivo imaging at higher resolution than is currently achievable with ultrasound, MRI or x-ray methods is needed across several fields of medicine. Potential applications include imaging of vascular tissue including plaque deposits, guidance of biopsy needles to aid in cancer diagnosis, and guidance tools for microsurgery. The specific objective of this SBIR project is the development of a high speed, high resolution optical method for in vivo vascular imaging to aid in the identification of vulnerable plaque. Heart disease is a leading cause of death in the United States. The study of, and ultimately the detection in patients, of those plaques most likely to cause heart attacks and strokes may allow timely intervention and provide direction in developing new treatments.